A groundbreaking milestone has been achieved in the realm of liver health: the U.S. Food and Drug Administration (FDA) has given its approval to Rezdiffra (resmetirom), marking the first-ever medication sanctioned to combat nonalcoholic steatohepatitis (NASH), a prevalent liver condition that often culminates in liver failure.
Characterized by the accumulation of fat in the liver, NASH, also known as metabolic dysfunction-associated steatohepatitis (MASH), emerges as a consequence of obesity or excess weight. It represents an advanced stage of nonalcoholic fatty liver disease (NAFLD), wherein inflammation and tissue damage gradually escalate, potentially leading to fibrosis—a precursor to cirrhosis or the need for liver transplantation.
The approval of Rezdiffra offers newfound hope to adults grappling with NASH, particularly those facing moderate to advanced liver scarring, or fibrosis. Administered alongside dietary and exercise regimens, this daily oral medication heralds a paradigm shift in managing liver damage associated with NASH.
Dr. Nikolay Nikolov, MD, acting director of the Office of Immunology and Inflammation at the FDA’s Center for Drug Evaluation and Research, hailed the approval as a watershed moment, emphasizing the long-awaited availability of a treatment specifically targeting liver damage in NASH patients.
Echoing this sentiment, Dr. Suzanne Sharpton, MD, an esteemed assistant professor and transplant hepatologist at Vanderbilt University Medical Center, lauded the significance of Rezdiffra’s approval in tackling NASH, a pervasive global health concern. She underscored the immense clinical value of a therapeutic intervention that not only addresses steatohepatitis but also tackles fibrosis—a pivotal advancement in the notoriously challenging landscape of NASH drug development.
Resmetirom Showed Impressive Trial Results for NASH
In a groundbreaking phase of clinical research detailed in The New England Journal of Medicine, a cohort of 966 individuals diagnosed with NASH, accompanied by fibrosis not yet advanced to cirrhosis, were assigned randomly to receive either an 80 mg or 100 mg daily dose of resmetirom or a placebo over the course of one year.
The study’s findings revealed a remarkable outcome: at the conclusion of the trial period, 30 percent of participants receiving the higher resmetirom dosage experienced a reduction in NASH severity by at least two points on an 8-point scale, coupled with no deterioration in fibrosis, contrasting sharply with the approximately 10 percent observed in the placebo group. Furthermore, significant improvements in fibrosis were noted, with 26 percent of patients on the 100 mg dose and 24 percent on the 80 mg dose showcasing marked improvement, compared to 14 percent in the placebo cohort.
“This suggests that resmetirom not only halts the progression of fibrosis but also holds promise in reversing it,” comments Dr. Jean-François Dufour, a researcher at the Centre Digestive for Diseases in Lausanne, Switzerland, who has delved into NASH and resmetirom, although not directly involved in this study.
While instances of diarrhea and nausea were more prevalent among resmetirom recipients compared to those on placebo, serious adverse effects were infrequent and consistent across all intervention groups.
Dr. Mary Rinella, a co-author of the study and a respected professor and transplant hepatologist at the Pritzker School of Medicine at the University of Chicago, emphasizes resmetirom’s safety profile and its unique ability to mitigate liver fibrosis—an attribute unparalleled by any other treatment option.
Given these promising results, medical practitioners may consider earlier screening of high-risk individuals for NASH and fibrosis, aiming to intervene before irreversible liver damage ensues, notes Dr. Ansaripour.
“The introduction of resmetirom as a therapeutic agent for NASH holds transformative potential, potentially reshaping treatment protocols and strategies,” Ansaripour asserts. “This may prompt revisions in clinical guidelines, advocating for proactive screening in primary care settings for NASH among high-risk populations, and advocating for a collaborative, multidisciplinary approach to disease management, centered around early intervention and prevention of disease progression.”